Metabolic risk factors can lead to heart disease, diabetes and stroke. Metabolic syndrome is becoming more common due to a rise in obesity rates in adults.
Type 2 diabetes (T2DM) afflicts 246 million people worldwide, including 21 million in the United States. Another 54 million Americans have pre-diabetes. If the incidence of T2DM continues to increase at the present rate, one in three Americans, and one in two minorities born in 2000 will develop diabetes in their lifetime (Cowie C, MMWR 52: 833-837, 2003). In addition to the human cost, direct medical costs associated with diabetes in the United States currently exceed $132 billion a year and consume ˜10% of health care costs in industrialized nations (Saltiel A R Cell 104: 517-529, 2001). Diabetes is the leading cause of both end stage renal disease and blindness (in people aged 20-74 years), and its association with cardiovascular disease increases mortality rates two-fold.
Although intensive genetic analyses of human populations have confirmed contributory roles for some specific genes, these cannot account—even in the aggregate—for powerful genetic predisposition T2DM. The link between obesity and diabetes is the result of obesity-related insulin resistance stress on the insulin-producing cells of the pancreas. Genetic differences and differences in numbers of insulin producing beta cells can cause differential susceptibility among individuals to T2DM. Therefore, there is a need to identify relevant genes associated with susceptibility to diabetes. This invention addresses this need and provides treatment strategies for manipulating beta cells and treating T2DM.